Camptothecin: a key building block in the design of anti-tumor agents

Camptothecin (CPT) is a naturally occurring alkaloid that plays a pivotal role in cancer chemotherapy owing to its potent inhibition of topoisomerase I.It was first isolated from Chinese Camptotheca acuminata shrub in the 1960s by Monroe Wall, and it is now used to treat cancers such as ovarian, colon, lung, and breast cancer [1].Early studies found that direct parenteral administration of CPT was unfeasible due to its poor solubility, and it faced challenges in clinical trials for colon cancer in 1970 because of the need for high doses [2].In addition, the E ring of CPT is susceptible to ring-opening and inactivation under physiological conditions.Binding of human serum albumin has also been found to induce E-ring opening, leading to hemorrhagic cystitis [3].Therefore, improvements in CPT therapy are necessary.This editorial examines recent developments in the study of CPT, with a particular focus on its small-molecule derivatives, structureactivity relationships (SARs), prodrugs, and antibody-drug conjugates (ADCs).Further expansion of these areas is essential to enhance the efficacy of CPT and overcome its limitations.